Acute organ transplant rejection is characterized by a heavy lymphocyte infiltration. We have previously shown that alterations in the graft endothelium lead to increased lymphocyte traffic into the graft. Here, we demonstrate that lymphocytes adhere to the endothelium of rejecting cardiac transplants, but not to the endothelium of syngeneic grafts or normal hearts analyzed with the in vitro Stamper-Woodruff binding assay. Concomitant with the enhanced lymphocyte adhesion, the cardiac endothelium begins to de novo express sialyl Lewis(a) and sialyl Lewis(x) (sLea and sLex) epitopes, which have been shown to be sequences of L-selectin counterreceptors. The endothelium of allografts, but not that of syngeneic grafts or normal controls, also reacted with the L-selectin-immunoglobulin G fusion protein, giving further proof of inducible L-selectin counterreceptors. The lymphocyte adhesion to endothelium could be significantly decreased either by treating the lymphocytes with anti-L-selectin antibody HRL-1, or by treating the tissue sections with sialidase or anti-sLea or anti-sLex monoclonal antibodies. Finally, we synthetized enzymatically several members of the sLex family oligosaccharides and analyzed their ability to block lymphocyte adhesion to cardiac endothelium. The monovalent sLex (a tetramer), divalent sLex (a decamer), and tetravalent sLex (a 22-mer) could all significantly reduce lymphocyte binding, but the inhibition by the tetravalent sLex-construct was clearly superior to other members of the sLex family. The crucial control oligosaccharides, sialyl lactosamines lacking fucose but being otherwise similar to the members of sLex family, had no effect on lymphocyte binding.
Article|
October 01 1995
De novo expression of endothelial sialyl Lewis(a) and sialyl Lewis(x) during cardiac transplant rejection: superior capacity of a tetravalent sialyl Lewis(x) oligosaccharide in inhibiting L-selectin-dependent lymphocyte adhesion.
J P Turunen,
J P Turunen
Haartman Institute Department of Bacteriology, University of Helsinki, Finland.
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M L Majuri,
M L Majuri
Haartman Institute Department of Bacteriology, University of Helsinki, Finland.
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A Seppo,
A Seppo
Haartman Institute Department of Bacteriology, University of Helsinki, Finland.
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S Tiisala,
S Tiisala
Haartman Institute Department of Bacteriology, University of Helsinki, Finland.
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T Paavonen,
T Paavonen
Haartman Institute Department of Bacteriology, University of Helsinki, Finland.
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M Miyasaka,
M Miyasaka
Haartman Institute Department of Bacteriology, University of Helsinki, Finland.
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K Lemström,
K Lemström
Haartman Institute Department of Bacteriology, University of Helsinki, Finland.
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L Penttilä,
L Penttilä
Haartman Institute Department of Bacteriology, University of Helsinki, Finland.
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O Renkonen,
O Renkonen
Haartman Institute Department of Bacteriology, University of Helsinki, Finland.
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R Renkonen
R Renkonen
Haartman Institute Department of Bacteriology, University of Helsinki, Finland.
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J P Turunen
Haartman Institute Department of Bacteriology, University of Helsinki, Finland.
M L Majuri
Haartman Institute Department of Bacteriology, University of Helsinki, Finland.
A Seppo
Haartman Institute Department of Bacteriology, University of Helsinki, Finland.
S Tiisala
Haartman Institute Department of Bacteriology, University of Helsinki, Finland.
T Paavonen
Haartman Institute Department of Bacteriology, University of Helsinki, Finland.
M Miyasaka
Haartman Institute Department of Bacteriology, University of Helsinki, Finland.
K Lemström
Haartman Institute Department of Bacteriology, University of Helsinki, Finland.
L Penttilä
Haartman Institute Department of Bacteriology, University of Helsinki, Finland.
O Renkonen
Haartman Institute Department of Bacteriology, University of Helsinki, Finland.
R Renkonen
Haartman Institute Department of Bacteriology, University of Helsinki, Finland.
Online ISSN: 1540-9538
Print ISSN: 0022-1007
J Exp Med (1995) 182 (4): 1133–1141.
Citation
J P Turunen, M L Majuri, A Seppo, S Tiisala, T Paavonen, M Miyasaka, K Lemström, L Penttilä, O Renkonen, R Renkonen; De novo expression of endothelial sialyl Lewis(a) and sialyl Lewis(x) during cardiac transplant rejection: superior capacity of a tetravalent sialyl Lewis(x) oligosaccharide in inhibiting L-selectin-dependent lymphocyte adhesion.. J Exp Med 1 October 1995; 182 (4): 1133–1141. doi: https://doi.org/10.1084/jem.182.4.1133
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